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DUODENOGASTRIC REFLUX OF BILE AND ASPIRIN-INDUCED GASTRIC DAMAGE IN MAN
601
COLONIC INVOLVEMENT IN SALMONELLOSIS
SIR,—We can confirm the findings of Mandal and Mani1 et al.2 The pathological and histological of colonic mucosa were investigated in 32 patients changes aged 14-74 with acute enterocolitis caused by Salmonella java
and
Appelbaum
(2), derby (1), agona (1), typhimurium (16), heidelberg (1), montevideo (1), oranienburg (1), thompson (1), bovis morbificans (1), enteritidis (5), kapemba (1), and napoli (1). Rectal tissue was obtained by suction biopsy. Slight symptoms and mild diarrhoea were observed in 3 patients, moderate diarrhoea (five to ten motions a day) in 13 patients, and severe diarrhoea (more than ten motions a day) in 16 patients. The sigmoidoscopic appearance was normal in 1 patient. In 14 the colonic mucosa showed mild inflammatory changes (mild hyperæmia, oedema and fragility). In 15 patients moderate inflammatory changes were seen (hyperæmia, oedema, fragility of the mucosa, granularity, and a few petechiæ). In 2 patients the colonic mucosa was severely inflamed with intense hyperæmia and severe mucosal fragility besides erosions and ulcerations.
Histologically, the colonic mucosa was normal or only slightly abnormal in 3 patients. In 19 specimens mild inflammatory changes were observed—i.e. mild hyperæmia, oedema, vascular congestion, and mild round-cell infiltration in the lamina propria. In 4 biopsy specimens the mucosa showed moderate inflammatory changes consisting in severe vascular congestion, œdema, interstitial haemorrhage, and moderate infiltration in the lamina propria with round cells and with polymorphonuclear cells. Biopsy specimens from 6 patients showed severe inflammatory changes (severe oedema, severe vascular congestion, infiltration in the lamina propria with round cells and with leucocytes, interstitial haemorrhage, abscesses in the lamina propria, crypt abscesses, and erosions and ulcerations in the epithelium of crypts and in the surface epithelium). All pathological findings in colonic mucosa were reversible. Treatment was symptomatic. In most patients the inflammatory changes disappeared in 5-13 days.
Hoard of Capsules.
tle
containing at least 95 capsules. Fewer than 100 capsules taken by the patient over the 22-year period before his death although over 3000 were dispensed. This case illustrates several significant points. The patient seemed to remain well even though he had not taken his medicine. The wife obtained further supplies of the drug even though she must have known that her husband was not taking his medicine. Because the patient did not ask to see his general practitioner, the general practitioner assumed that the prescribed medication was being taken regularly and that it was proving beneficial. Perhaps the patient continued to obtain regular supplies were
because he was worried about how his doctor would react if he found out that his patient was not following instructions. Pharmaceutical Department, North Manchester General Hospital, Manchester M8 6RB
L. A. GOLDBERG
These data confirm the view of Mandal and Mani that colonic involvement is common in human salmonellosis. Department of Infectious Diseases, ALE ALENKA RADSEL-MEDVESCEK University Hospital of Ljubljana, and obiology, R. ZARGI Departments of Pathology and Microbiology, Faculty of Medicine, M. AĆKO University of Ljubljana, JADRANKA ZAJC-SATLER Ljubljana, Yugoslavia
DUODENOGASTRIC REFLUX OF BILE AND ASPIRIN-INDUCED GASTRIC DAMAGE IN MAN
SIR,-Aspirin
may
damage gastric mucosa in
man,
causing
erosions, chronic peptic ulcer, and upper gastrointestinal haemorrhage.1 However, hospital admission for this reason is acute
the rates being 15 for bleeding and 10 for gastric ulcer per 100 000 users per years This discrepancy between the scale of aspirin consumption and the incidence of gastrointestinal side-effects is not explained. Reflux into the stomach of bile and duodenal contents may play an important role in the pathogenesis of gastritis and gastric ulcer,3 and bile acids, like acetylsalicylic acid, are potent breakers of the gastric mucosal barrier.4 In the rat simultaneous oral administration of bile or bile acids and aspirin significantly increased the incidence of gastric mucosal bleeding and ulceration compared with the administration of aspirin alone.56 The fall of transmucosal electrical potential difference in man after ingestion of aspirin and taurocholic acid was significantly longer than that found after aspirin or taurocholic acid atone.7 We have tried to determine if the presence of bile in the stomach increases the risk of gastric damage after aspirin ingestion in man. We studied endoscopically two groups of patients regularly taking aspirin-containing drugs (0-50-3 g/day): 18 not common,
A HOARD OF CAPSULES ILLUSTRATING PATIENT NON-COMPLIANCE
SiR,—The Department of Health is concerned about the inin cost of supplying medication to patients. Comments have been made in the mass media regarding overprescribing, patient non-compliance, the high cost of drugs, and the wastage of such medicines. The following case illustrates the crease
problems. For several years before his death a man with bronchial asthma had been prescribed ’Amesec’ (aminophylline, ephe-
drine, and amylobarbitone) by
his general practitioner. Each month his wife collected from the health centre a new prescription for 100 capsules. The prescription was dispensed at the local pharmacy. The patient remained fairly well for three years before his death, from a cause unrelated to asthma, and he did not visit his general practitioner on any occasion. After her husband’s death, his wife wished to remove the unused medicines (a DUMP campaign had recently be successfully concluded in the area), and these unwanted medicines found their way to the hospital pharmacy. Thirty-one bottles (see figure) containing 3006 capsules were returned, each bot1. Mandal, B. K., Mani, V. Lancet, 1976, i, 887. 2. Appelbaum, P. C., Scragg, J., Schonland, M. M. ibid. 1976, ii, 102.
1. 2. 3. 4. 5. 6. 7.
Cooke, A. R. Am. J. dig. Dis. 1976, 21, 155. Levy, M. New Engl. J. Med. 1974, 290, 1158. Rees, W., Rhodes, J. Clins Gastroent. 1977, 6, 179. Ivey, K. J. Gastroenterology, 1971, 61, 247. Djahanguiri, B., Abtahi, F. S., Hemmati, M. ibid. 1973, 65, 630. Semple, P. F., Russel, R. I. ibid. 1975, 68, 67. Cochran, K. M., Mackenzie, J. F., Russel, R. I. Br. med. J. 1975, i, 183.
602
(GROUP 1) OR WITHOUT (GROUP 2) ASPIRIN-ASSOCIATED GASTRIC DAMAGE
BILE STAINING IN PATIENTS WITH
with acute upper gastrointestinal bleeding (excluding chronic gastric ulcer and duodenal lesions) (group 1); 20 patients without signs of gastroduodenal disease or blood-loss (group 2). The two groups were comparable with regard to age and sex, type of disease treated with aspirin, form and total dose of aspirin, daily consumption of alcohol, and haemostasis. Endoscopic preparation was with 1% tetracaine gargle only. The ACMI 7089 P panendoscope was used. In the group 1, endoscopy within two days of bleeding showed single or multiple antral erosions in 16 cases and multiple fundic erosions in 4. In the group 2, the gastric mucosa was apparently normal in 14 cases and congestive in 6. In the two groups, presence or absence of duodenogastric reflux of bile was evaluated by the determination of the colour of the mucous lake--clear or mildly, moderately, or heavily bile (green) stained. The accuracy of this visual judgment of the amount of bile in the stomach has been demonstrated by plotting the degree of bile staining against the actual gastric bile acid concentration: moderate and heavy staining, when compared to clear or mild staining, reflected significant increase in bile-acid concentration.8 In our study, duodenogastric reflux of bile was observed in 15 patients in the group 1 and in 5 patients in the group 2 (p<0-01). The frequence of moderately or heavy bile-staining lake was significantly higher in group 1 than in group 2
patients
(table). No correlation was found between the importance of the reflux and the number of acute mucosal erosions. The results of this endoscopic study suggest that the coincidence of aspirin ingestion with duodenogastric reflux of bile may be a factor in the pathogenesis of aspirin-induced gastric mucosal damage in some patients.
duodenogastric
Clinique Médicale A, Centre Hospitalier Universitaire, 80030 Amiens, France
JEAN-PIERRE CAPRON JEAN-LOUIS DUPAS JEAN-PAUL JOLY ALFRED LORRIAUX
ORAL CONTRACEPTIVES AND ENDOMETRIAL CARCINOMA: CASE FOR PROGESTERONE-RECEPTOR DEFECT
SIR,-Endometrial carcinoma
in young women complicatoral contraceptionl-3 is an anomaly. We would like to report such a case and to discuss the likely pathogenesis in order to define the logical basis for treatment. A 33-year-old para 2 was referred with a 3-month history of menorrhagia and intermenstrual bleeding. She had been on oral contraception continuously for the preceding 7 years-’Norlestrin’ (norethisterone+ethinyla:stradiol), for 18 months, then Serial-28 (ethinyloestradiol and megestrol) and finally ’Serial-C’. On examination there was a bulky uterus. Curettage produced abundant tissue, and histological examination showed highly differentiated adenocarcinoma with some isolated areas normal except for oral-contraceptive effect. Extrafascial hysterectomy and bilateral salpingooophorectomy were performed. The carcinoma occupied most of the endome-
ing
8. 1. 2. 3.
Goldner, F. H., Boyce, H. W., Jr, Gastrointest. Endosc. 1976, 22, 197. Lyon, F. A. Am. J. Obstet. Gynec. 1975, 123, 299. Silverberg, S. G., Makowski, E. L. Obstet. Gynec. 1975, 46, 503. Kelley, H. W., Miles, P. A., Buster, J. E., Scragg, W. H. ibid. 1976, 47, 200.
was no myometrial invasion or extension to the cervix. Postoperatively radium was administered to the vagina. She is well, four years later. Oestrogen causes proliferation and hyperplasia of the endometrium, up to and including atypical adenomatous hyperprogression to neoplasia.4 By so setting the stage for further is a it is that necessary, though plasia, highly likely cestrogen probably insufficient, cause of endometrial adenocarcinoma. The, regular provision and withdrawal of progesterone may be supposed to protect the endometrium from these consequences of oestrogen action, so endometrial carcinoma women with normal menstrual cycles’ and in women on either the combined or sequential form of oral contraception is an anomaly which
triune, but there
requires explanation. The major action of all the sex steroids at a cellular level is the induction of protein synthesis, and for the initiation of this action the steroid must bind to a specific polypeptide receptor in the cytoplasm.6 Receptors which have been characterised include the progesterone receptor. Tissue progesterone receptors are normally induced by cestrogens.8 If progesterone receptors were deficient or absent in an area of endometrium, that area would be under the sole influence of oestrogen, endogenous or exogenous, and could be expected to show the same range of hyperplastic changes seen with anovulatory cycles and unopposed oestrogen action, irrespective of circulating progestagens. Circumstantial evidence for such localised receptor deficiences exists in the old and quite frequent observation of islands of proliferative endometrium that fail to undergo secretory conversion in the progesteronedominated luteal phase of normal cycles.9 The free cytoplasmic cestradiol and progesterone receptor content of the endometrium has been determined in several conditions by measuring the uptake of tritiated steroid by the cytosol fraction of tissue homogenates. 10-12 By ignoring steroid-receptor complexes (including the complexes still in the cytoplasm and those which have translocated to the nucleus) such assays estimate only what could be called the latent recq tor capacity: measuring in reality not what the steroid is doing at any instant, but rather what it is not doing. Even total receptor population assays7 (measuring both free and bound receptors irrespective of location) fail to indicate steroid-receptor turnover-rate-and so, by inference, receptor activity-in situations where hormone levels are changing, because not only is time required for receptors to be replenished after a hormone surge but also the resynthesis-rate varies under different conditions.12 So it is not surprising that discrepancies have been reported in the concentration of unbound endometrial receptors." 12 Nevertheless, in absolute terms, the presence or absence of receptors can be very useful information. Among highly differentiated endometrial carcinomas, it is significant that some have been shown to contain no demonstrable progesterone receptors while in others such receptors are abundant." It could be expected that highly differentiated carcinomas arising in situations of anovulation with no endogenous progesterone (a complication to which such women are prone" 14) would be the tumours with progesterone receptors, and histologically identical carcinomas arising in normally cycling women or women on oral contraception (both quite rare) would comprise the group with no progesterone receptors; but these associGusberg, S. B. ibid. 1967, 30, 287. Jones, H. O., Brewer, J. I. Am. J. Obstet. Gynec. 1941, 42, 1322. Chan, L., O’Malley, B. W. New Engl. J. Med. 1976, 294, 1322. Smith, R. G., Iramam, C. A., Buttram, V. C., O’Malley, B. W. Nature, 1975, 253, 271. 8. Milgrom, E., Luu Thi, M., Baulieu, E. E. in 6th Karolinska Symposium on Research Methods in Reproductive Endocrinology; p. 380. Geneva, 1973 9. Novak, E., Martzloff, K. H. Am. J. Obstet. Gynec. 1924, 8, 385. 10. Haukkamaa, M., Karjalainen, O., Luukainen, T. ibid. 1971, 111, 205. 11. Evans, L. H., Martin, J. D., Hähnel, R. J. clin. Endocr. Metab 1973, 38, 4. 5. 6. 7.
23. 12. Pollow,
K., Lübbert, H., Bcquoi, E., Kreuzer, G., Pollow, B. Endocrinology, 1975, 96, 319. 13. Peterson, E. P. Obstet. Gynec. 1968, 31, 702. 14. Lucas, W. E. Obstet. gynec. Surv. 1974, 29, 507.
COLONIC INVOLVEMENT IN SALMONELLOSIS
SIR,—We can confirm the findings of Mandal and Mani1 et al.2 The pathological and histological of colonic mucosa were investigated in 32 patients changes aged 14-74 with acute enterocolitis caused by Salmonella java
and
Appelbaum
(2), derby (1), agona (1), typhimurium (16), heidelberg (1), montevideo (1), oranienburg (1), thompson (1), bovis morbificans (1), enteritidis (5), kapemba (1), and napoli (1). Rectal tissue was obtained by suction biopsy. Slight symptoms and mild diarrhoea were observed in 3 patients, moderate diarrhoea (five to ten motions a day) in 13 patients, and severe diarrhoea (more than ten motions a day) in 16 patients. The sigmoidoscopic appearance was normal in 1 patient. In 14 the colonic mucosa showed mild inflammatory changes (mild hyperæmia, oedema and fragility). In 15 patients moderate inflammatory changes were seen (hyperæmia, oedema, fragility of the mucosa, granularity, and a few petechiæ). In 2 patients the colonic mucosa was severely inflamed with intense hyperæmia and severe mucosal fragility besides erosions and ulcerations.
Histologically, the colonic mucosa was normal or only slightly abnormal in 3 patients. In 19 specimens mild inflammatory changes were observed—i.e. mild hyperæmia, oedema, vascular congestion, and mild round-cell infiltration in the lamina propria. In 4 biopsy specimens the mucosa showed moderate inflammatory changes consisting in severe vascular congestion, œdema, interstitial haemorrhage, and moderate infiltration in the lamina propria with round cells and with polymorphonuclear cells. Biopsy specimens from 6 patients showed severe inflammatory changes (severe oedema, severe vascular congestion, infiltration in the lamina propria with round cells and with leucocytes, interstitial haemorrhage, abscesses in the lamina propria, crypt abscesses, and erosions and ulcerations in the epithelium of crypts and in the surface epithelium). All pathological findings in colonic mucosa were reversible. Treatment was symptomatic. In most patients the inflammatory changes disappeared in 5-13 days.
Hoard of Capsules.
tle
containing at least 95 capsules. Fewer than 100 capsules taken by the patient over the 22-year period before his death although over 3000 were dispensed. This case illustrates several significant points. The patient seemed to remain well even though he had not taken his medicine. The wife obtained further supplies of the drug even though she must have known that her husband was not taking his medicine. Because the patient did not ask to see his general practitioner, the general practitioner assumed that the prescribed medication was being taken regularly and that it was proving beneficial. Perhaps the patient continued to obtain regular supplies were
because he was worried about how his doctor would react if he found out that his patient was not following instructions. Pharmaceutical Department, North Manchester General Hospital, Manchester M8 6RB
L. A. GOLDBERG
These data confirm the view of Mandal and Mani that colonic involvement is common in human salmonellosis. Department of Infectious Diseases, ALE ALENKA RADSEL-MEDVESCEK University Hospital of Ljubljana, and obiology, R. ZARGI Departments of Pathology and Microbiology, Faculty of Medicine, M. AĆKO University of Ljubljana, JADRANKA ZAJC-SATLER Ljubljana, Yugoslavia
DUODENOGASTRIC REFLUX OF BILE AND ASPIRIN-INDUCED GASTRIC DAMAGE IN MAN
SIR,-Aspirin
may
damage gastric mucosa in
man,
causing
erosions, chronic peptic ulcer, and upper gastrointestinal haemorrhage.1 However, hospital admission for this reason is acute
the rates being 15 for bleeding and 10 for gastric ulcer per 100 000 users per years This discrepancy between the scale of aspirin consumption and the incidence of gastrointestinal side-effects is not explained. Reflux into the stomach of bile and duodenal contents may play an important role in the pathogenesis of gastritis and gastric ulcer,3 and bile acids, like acetylsalicylic acid, are potent breakers of the gastric mucosal barrier.4 In the rat simultaneous oral administration of bile or bile acids and aspirin significantly increased the incidence of gastric mucosal bleeding and ulceration compared with the administration of aspirin alone.56 The fall of transmucosal electrical potential difference in man after ingestion of aspirin and taurocholic acid was significantly longer than that found after aspirin or taurocholic acid atone.7 We have tried to determine if the presence of bile in the stomach increases the risk of gastric damage after aspirin ingestion in man. We studied endoscopically two groups of patients regularly taking aspirin-containing drugs (0-50-3 g/day): 18 not common,
A HOARD OF CAPSULES ILLUSTRATING PATIENT NON-COMPLIANCE
SiR,—The Department of Health is concerned about the inin cost of supplying medication to patients. Comments have been made in the mass media regarding overprescribing, patient non-compliance, the high cost of drugs, and the wastage of such medicines. The following case illustrates the crease
problems. For several years before his death a man with bronchial asthma had been prescribed ’Amesec’ (aminophylline, ephe-
drine, and amylobarbitone) by
his general practitioner. Each month his wife collected from the health centre a new prescription for 100 capsules. The prescription was dispensed at the local pharmacy. The patient remained fairly well for three years before his death, from a cause unrelated to asthma, and he did not visit his general practitioner on any occasion. After her husband’s death, his wife wished to remove the unused medicines (a DUMP campaign had recently be successfully concluded in the area), and these unwanted medicines found their way to the hospital pharmacy. Thirty-one bottles (see figure) containing 3006 capsules were returned, each bot1. Mandal, B. K., Mani, V. Lancet, 1976, i, 887. 2. Appelbaum, P. C., Scragg, J., Schonland, M. M. ibid. 1976, ii, 102.
1. 2. 3. 4. 5. 6. 7.
Cooke, A. R. Am. J. dig. Dis. 1976, 21, 155. Levy, M. New Engl. J. Med. 1974, 290, 1158. Rees, W., Rhodes, J. Clins Gastroent. 1977, 6, 179. Ivey, K. J. Gastroenterology, 1971, 61, 247. Djahanguiri, B., Abtahi, F. S., Hemmati, M. ibid. 1973, 65, 630. Semple, P. F., Russel, R. I. ibid. 1975, 68, 67. Cochran, K. M., Mackenzie, J. F., Russel, R. I. Br. med. J. 1975, i, 183.
602
(GROUP 1) OR WITHOUT (GROUP 2) ASPIRIN-ASSOCIATED GASTRIC DAMAGE
BILE STAINING IN PATIENTS WITH
with acute upper gastrointestinal bleeding (excluding chronic gastric ulcer and duodenal lesions) (group 1); 20 patients without signs of gastroduodenal disease or blood-loss (group 2). The two groups were comparable with regard to age and sex, type of disease treated with aspirin, form and total dose of aspirin, daily consumption of alcohol, and haemostasis. Endoscopic preparation was with 1% tetracaine gargle only. The ACMI 7089 P panendoscope was used. In the group 1, endoscopy within two days of bleeding showed single or multiple antral erosions in 16 cases and multiple fundic erosions in 4. In the group 2, the gastric mucosa was apparently normal in 14 cases and congestive in 6. In the two groups, presence or absence of duodenogastric reflux of bile was evaluated by the determination of the colour of the mucous lake--clear or mildly, moderately, or heavily bile (green) stained. The accuracy of this visual judgment of the amount of bile in the stomach has been demonstrated by plotting the degree of bile staining against the actual gastric bile acid concentration: moderate and heavy staining, when compared to clear or mild staining, reflected significant increase in bile-acid concentration.8 In our study, duodenogastric reflux of bile was observed in 15 patients in the group 1 and in 5 patients in the group 2 (p<0-01). The frequence of moderately or heavy bile-staining lake was significantly higher in group 1 than in group 2
patients
(table). No correlation was found between the importance of the reflux and the number of acute mucosal erosions. The results of this endoscopic study suggest that the coincidence of aspirin ingestion with duodenogastric reflux of bile may be a factor in the pathogenesis of aspirin-induced gastric mucosal damage in some patients.
duodenogastric
Clinique Médicale A, Centre Hospitalier Universitaire, 80030 Amiens, France
JEAN-PIERRE CAPRON JEAN-LOUIS DUPAS JEAN-PAUL JOLY ALFRED LORRIAUX
ORAL CONTRACEPTIVES AND ENDOMETRIAL CARCINOMA: CASE FOR PROGESTERONE-RECEPTOR DEFECT
SIR,-Endometrial carcinoma
in young women complicatoral contraceptionl-3 is an anomaly. We would like to report such a case and to discuss the likely pathogenesis in order to define the logical basis for treatment. A 33-year-old para 2 was referred with a 3-month history of menorrhagia and intermenstrual bleeding. She had been on oral contraception continuously for the preceding 7 years-’Norlestrin’ (norethisterone+ethinyla:stradiol), for 18 months, then Serial-28 (ethinyloestradiol and megestrol) and finally ’Serial-C’. On examination there was a bulky uterus. Curettage produced abundant tissue, and histological examination showed highly differentiated adenocarcinoma with some isolated areas normal except for oral-contraceptive effect. Extrafascial hysterectomy and bilateral salpingooophorectomy were performed. The carcinoma occupied most of the endome-
ing
8. 1. 2. 3.
Goldner, F. H., Boyce, H. W., Jr, Gastrointest. Endosc. 1976, 22, 197. Lyon, F. A. Am. J. Obstet. Gynec. 1975, 123, 299. Silverberg, S. G., Makowski, E. L. Obstet. Gynec. 1975, 46, 503. Kelley, H. W., Miles, P. A., Buster, J. E., Scragg, W. H. ibid. 1976, 47, 200.
was no myometrial invasion or extension to the cervix. Postoperatively radium was administered to the vagina. She is well, four years later. Oestrogen causes proliferation and hyperplasia of the endometrium, up to and including atypical adenomatous hyperprogression to neoplasia.4 By so setting the stage for further is a it is that necessary, though plasia, highly likely cestrogen probably insufficient, cause of endometrial adenocarcinoma. The, regular provision and withdrawal of progesterone may be supposed to protect the endometrium from these consequences of oestrogen action, so endometrial carcinoma women with normal menstrual cycles’ and in women on either the combined or sequential form of oral contraception is an anomaly which
triune, but there
requires explanation. The major action of all the sex steroids at a cellular level is the induction of protein synthesis, and for the initiation of this action the steroid must bind to a specific polypeptide receptor in the cytoplasm.6 Receptors which have been characterised include the progesterone receptor. Tissue progesterone receptors are normally induced by cestrogens.8 If progesterone receptors were deficient or absent in an area of endometrium, that area would be under the sole influence of oestrogen, endogenous or exogenous, and could be expected to show the same range of hyperplastic changes seen with anovulatory cycles and unopposed oestrogen action, irrespective of circulating progestagens. Circumstantial evidence for such localised receptor deficiences exists in the old and quite frequent observation of islands of proliferative endometrium that fail to undergo secretory conversion in the progesteronedominated luteal phase of normal cycles.9 The free cytoplasmic cestradiol and progesterone receptor content of the endometrium has been determined in several conditions by measuring the uptake of tritiated steroid by the cytosol fraction of tissue homogenates. 10-12 By ignoring steroid-receptor complexes (including the complexes still in the cytoplasm and those which have translocated to the nucleus) such assays estimate only what could be called the latent recq tor capacity: measuring in reality not what the steroid is doing at any instant, but rather what it is not doing. Even total receptor population assays7 (measuring both free and bound receptors irrespective of location) fail to indicate steroid-receptor turnover-rate-and so, by inference, receptor activity-in situations where hormone levels are changing, because not only is time required for receptors to be replenished after a hormone surge but also the resynthesis-rate varies under different conditions.12 So it is not surprising that discrepancies have been reported in the concentration of unbound endometrial receptors." 12 Nevertheless, in absolute terms, the presence or absence of receptors can be very useful information. Among highly differentiated endometrial carcinomas, it is significant that some have been shown to contain no demonstrable progesterone receptors while in others such receptors are abundant." It could be expected that highly differentiated carcinomas arising in situations of anovulation with no endogenous progesterone (a complication to which such women are prone" 14) would be the tumours with progesterone receptors, and histologically identical carcinomas arising in normally cycling women or women on oral contraception (both quite rare) would comprise the group with no progesterone receptors; but these associGusberg, S. B. ibid. 1967, 30, 287. Jones, H. O., Brewer, J. I. Am. J. Obstet. Gynec. 1941, 42, 1322. Chan, L., O’Malley, B. W. New Engl. J. Med. 1976, 294, 1322. Smith, R. G., Iramam, C. A., Buttram, V. C., O’Malley, B. W. Nature, 1975, 253, 271. 8. Milgrom, E., Luu Thi, M., Baulieu, E. E. in 6th Karolinska Symposium on Research Methods in Reproductive Endocrinology; p. 380. Geneva, 1973 9. Novak, E., Martzloff, K. H. Am. J. Obstet. Gynec. 1924, 8, 385. 10. Haukkamaa, M., Karjalainen, O., Luukainen, T. ibid. 1971, 111, 205. 11. Evans, L. H., Martin, J. D., Hähnel, R. J. clin. Endocr. Metab 1973, 38, 4. 5. 6. 7.
23. 12. Pollow,
K., Lübbert, H., Bcquoi, E., Kreuzer, G., Pollow, B. Endocrinology, 1975, 96, 319. 13. Peterson, E. P. Obstet. Gynec. 1968, 31, 702. 14. Lucas, W. E. Obstet. gynec. Surv. 1974, 29, 507.